A5078356634- Advanced Drug Delivery Systems
- Drug Solubulity and Delivery Systems
- Drug Transport and Resistance Mechanisms
- Diabetes Treatment and Management
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Pancreatic function and diabetes
- Barrier Structure and Function Studies
- Inhalation and Respiratory Drug Delivery
- Biochemical Analysis and Sensing Techniques
- Advanced Glycation End Products research
- Ion channel regulation and function
- Diabetes Management and Research
- RNA Interference and Gene Delivery
- Analytical Methods in Pharmaceuticals
- Cancer-related molecular mechanisms research
- Amino Acid Enzymes and Metabolism
- Pleural and Pulmonary Diseases
- Neuropeptides and Animal Physiology
- 3D Printing in Biomedical Research
- Immunotherapy and Immune Responses
- Ion Transport and Channel Regulation
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Cancer-related gene regulation
- Ion Channels and Receptors
Novo Nordisk (Denmark)
2015-2025
Massachusetts Institute of Technology
2021
Novo Nordisk (United States)
2020
Trinity College Dublin
2009-2015
University of Southern Denmark
2011-2013
Semaglutide, a glucagon-like peptide 1 (GLP-1) analog, induces weight loss, lowers glucose levels, and reduces cardiovascular risk in patients with diabetes. Mechanistic preclinical studies suggest loss is mediated through GLP-1 receptors (GLP-1Rs) the brain. The findings presented here show that semaglutide modulated food preference, reduced intake, caused without decreasing energy expenditure. Semaglutide directly accessed brainstem, septal nucleus, hypothalamus but did not cross...
An orally delivered GLP-1 analog coformulated with the absorption enhancer SNAC achieves transcellular-directed in stomach.
Delivering fragile drugs to the gut Oral delivery is simplest and least invasive way deliver many pharmaceuticals, but medications, including insulin, cannot survive passage through stomach or gastrointestinal tract. Abramson et al. developed an ingestible vehicle that could self-reorient from any starting position so as attach gastric wall. Encapsulation of a spring in sugar casing allowed for triggered actuation biomolecules. The approach successfully provided active insulin pigs. Science...
More than 15 years have passed since the first description of unbound brain-to-plasma partition coefficient (Kp,uu,brain) by Prof. Margareta Hammarlund-Udenaes, which was enabled advancements in experimental methodologies including cerebral microdialysis. Since then, growing knowledge and data continue to support notion that (free) concentration a drug at site action, such as brain, is driving force for pharmacological responses. Towards this end, Kp,uu,brain key parameter obtain brain...
Fast-acting insulin aspart (faster aspart) is a novel formulation of containing two additional excipients: niacinamide, to increase early absorption, and L-arginine, optimize stability. The aim this study was evaluate the impact niacinamide on absorption investigate mechanism action underlying accelerated absorption.The assessed in pharmacokinetic analyses pigs humans, small angle X-ray scattering experiments, trans-endothelial transport assays, vascular tension measurements, subcutaneous...
Semaglutide is the first oral glucagon-like peptide-1 (GLP-1) analog commercially available for treatment of type 2 diabetes. In this work, semaglutide was incorporated into poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NPs) to improve its delivery across intestinal barrier. The nanocarriers were surface-decorated with either a peptide or an affibody that target human neonatal Fc receptor (hFcRn), located on luminal cell surface enterocytes. Both ligands...
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders that characterized by cytoplasmic aggregates nuclear clearance of TAR DNA-binding protein 43 (TDP-43). Studies in Drosophila, zebrafish mouse demonstrate the neuronal dysfunction TDP-43 is causally related to disease formation. However, also observed glia muscle cells, which equally affected ALS FTLD; yet, it unclear whether glia- or muscle-specific contributes pathogenesis. Here,...
Abstract Peptides play important roles in regulating biological processes and form the basis of a multiplicity therapeutic drugs. To date, only about 300 peptides human have confirmed bioactivity, although tens thousands been reported literature. The majority these are inactive degradation products endogenous proteins peptides, presenting needle-in-a-haystack problem identifying most promising candidate from large-scale peptidomics experiments to test for bioactivity. address this challenge,...
Needle-based injections currently enable the administration of a wide range biomacromolecule therapies across body, including gastrointestinal tract1–3, through recent developments in ingestible robotic devices4–7. However, needles generally require training, sharps management and disposal, pose challenges for autonomous systems. Here, inspired by jetting systems cephalopods, we have developed evaluated microjet delivery that can deliver jets axial radial directions into tissue, making them...
Abstract Evidence suggests epithelial–mesenchymal transition (EMT) as one potential source of fibroblasts in idiopathic pulmonary fibrosis. To assess the contribution alveolar epithelial cell (AEC) EMT to fibroblast accumulation vivo following lung injury and influence extracellular matrix on AEC phenotype vitro , Nkx2.1‐Cre;mT/mG mice were generated which AECs permanently express green fluorescent protein (GFP). On days 17–21 intratracheal bleomycin administration, ∼4% GFP‐positive...
Fibrosis of the lung is characterized by accumulation myofibroblasts, a key mediator in fibrogenic reaction. Cumulative evidence indicates that epithelial-mesenchymal transition (EMT), process whereby epithelial cells become mesenchyme-like, an important contributing source for myofibroblast population. Underlying this phenotypical change dramatic alteration cellular structure. The receptor advanced glycation end-products (RAGE) has been suggested to maintain homeostasis mediating cell...
Insulin and its receptor are known to be present functional in the brain. cerebrospinal fluid concentrations have been shown correlate with plasma levels of insulin a nonlinear fashion, indicative saturable transport pathway from blood brain interstitial fluid. The aim study was investigate whether transported across endothelial cells vitro via an receptor-dependent pathway. showed that expressed at both mRNA protein bovine cells. Luminally applied radiolabeled receptor-mediated binding This...
The purpose of the present study was to investigate interaction intestinal permeation enhancers with lipid and surfactant components in milieu small intestine. Maltosides different chain lengths (decyl-, dodecyl-, tetradecyl-maltoside; DM, DDM, TDM, respectively) were used as examples nonionic, surfactant-like enhancers, their effect on FD4 across Caco-2 monolayers monitored. To mimic environment intestine, modified versions fasted fed state simulated fluid (FaSSIFmod, FeSSIFmod6.5, addition...
Despite extensive research, targeted delivery of substances to the brain still poses a great challenge due selectivity blood-brain barrier (BBB). Most molecules require either carrier- or receptor-mediated transport systems reach central nervous system (CNS). These form attractive routes for therapeutics into CNS, yet number known endothelium-enriched receptors allowing large is scarce. Therefore, identify novel BBB targets, we combined transcriptomic analysis human and murine endothelium...
Peroxisome proliferator activated receptor γ (PPARγ) agonists are effective antifibrotic agents in a number of tissues. Effects these on epithelial-mesenchymal transition (EMT) primary alveolar epithelial cells (AEC) and potential mechanisms underlying effects EMT have not been well delineated. We examined troglitazone, synthetic PPARγ agonist, transforming growth factor (TGF)-β1-induced rat AEC an type II (AT2) cell line (RLE-6TN). TGF-β1 (2.5 ng/mL) induced both types, as evidenced by...